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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A
Mei-Zhu Shen, Yong Zhang, Fang Wu, Mei-Zhen Shen, Jun-Lin Liang, Xiao-Long Zhang, Xiao-Jian Liu, Xin-Shu Li, Ren-Sheng Wang
Mei-Zhu Shen, Yong Zhang, Fang Wu, Ren-Sheng Wang, Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Mei-Zhen Shen, Department of Radiotherapy, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Jun-Lin Liang, Xiao-Long Zhang, Xiao-Jian Liu, Department of Colorectal Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Xin-Shu Li, Department of Clinical Medicine, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Shen MZ, Zhang Y, and Wang RS conceived and designed the experiments; Wu F, Shen MZ, Liang JL, Zhang XL, Liu XJ, and Li XS performed the experiments; Shen MZ and Wang RS analyzed the data and wrote the manuscript; all authors read and approved the final manuscript.
Institutional animal care and use committee statement: This study was reviewed and approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (Approval No. 2023-E386-01).
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ren-Sheng Wang, PhD, Doctor, Department of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning 530021, Guangxi Zhuang Autonomous Region, China. 13807806008@163.com
Received: December 5, 2023
Peer-review started: December 5, 2023
First decision: December 18, 2023
Revised: December 31, 2023
Accepted: February 2, 2024
Article in press: February 2, 2024
Published online: April 15, 2024
Processing time: 127 Days and 19.5 Hours
BACKGROUND
Radiotherapy stands as a promising therapeutic modality for colorectal cancer (CRC); yet, the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.
AIM
To elucidate the role played by microRNA-298 (miR-298) in CRC radio-resistance.
METHODS
To establish a radio-resistant CRC cell line, HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period. The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR, and protein expression determination was realized through Western blotting. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay. Radio-induced apoptosis was discerned through flow cytometry analysis.
RESULTS
We observed a marked upregulation of miR-298 in radio-resistant CRC cells. MiR-298 emerged as a key determinant of cell survival following radiation exposure, as its overexpression led to a notable reduction in radiation-induced apoptosis. Intriguingly, miR-298 expression exhibited a strong correlation with CRC cell viability. Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A (DYRK1A) as miR-298’s direct target.
CONCLUSION
Taken together, our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation, thereby positioning miR-298 as a promising candidate for mitigating radio-resistance in CRC.
Core Tip: Our findings indicate that microRNA-298 (miR-298) is upregulated in radio-resistant colorectal cancer (CRC) cells. Overexpression of miR-298 leads to decreased human dual-specificity tyrosine(Y)-regulated kinase 1A expression, ultimately enhancing the radio-resistance of CRC cells.
